Altered mitochondrial response to activation of T-cells in neonate

Abstract

Mitochondrial functions have a major impact on T-cell functionality. In this study we characterized whether mitochondrial function in the neonatal T-cells differs from that in the adult T-cells during short T-cell activation. Methods: We used flow cytometry methods to test mitochondrial mass and to monitor mitochondrial Ca 2+ levels, mitochondrial potential and superoxide generation in parallel with cytoplasmic Ca 2+ levels during phythohaemagglutinine-induced activation of CD4+ and CD8+ T-cells of 12 term neonates and 11 healthy adults. Results: Baseline mitochondrial mass of CD4+ and CD8+ cells was lower in the neonate than in the adult. In comparison with the adult, neonatal resting CD4+ T-cells had lower cytoplasmic Ca 2+ levels and this was associated with normal activation induced Ca 2+ -response. During short-term activation cytoplasmic Ca 2+-response was lower in neonatal than in adult CD8+ T-cells. Mitochondrial Ca 2+ uptake was increased in CD4+ neonatal T cells while it decreased in CD8+ T-cells. Mitochondrial depolarization was increased in CD4+ and decreased in CD8+ neonatal T-cells compared to adults. Superoxide generation was higher and equal in neonatal CD4+ and CD8+ cells, respectively, compared to the adult ones. Conclusion: Our data suggest that neonatal T-cells exhibit marked differences in mitochondrial function and superoxide generation compared to adult T-cells.

Dissecting the defects in the neonatal CD8+ T-cell response

“…). Increased T‐cell production of ROS, coupled with neonates’ diminished free‐radical scavenging capabilities, damages the lung . Prolonged recruitment and survival of neutrophils due to increased IL‐8 from neonatal T cells plays a role in tissue damage in the lungs .…”

“…Increased T-cell production of ROS, coupled with neonates' diminished free-radical scavenging capabilities, damages the lung. 99 Prolonged recruitment and survival of neutrophils due to increased IL-8 from neonatal T cells plays a role in tissue damage in the lungs. 97,100 Infants who develop acute lung injury have been shown to have a higher level of IL-6 and increased CD8:CD4 ratio in the lung during injury and infection.…”

An Immunological Perspective on Neonatal Sepsis

“…This hypothesis is supported by several primary metabolic differences that have been described between neonates born prematurely, at term, and adults. For instance, during fetal life, mitochondria have a fragmented appearance [84], reduced mass [85], and display a more limited capacity for energy production [86]. In addition, preterm neonates exhibit increased lipid metabolism relative to their glycolytic activity [87]; this is linked to an altered metabolic response during sepsis [88].…”

An altered metabolism could contribute to the low activation of neonatal CD8+T cells

“…CD8 + T cells from newborns have distinct transcriptional and epigenetic profiles biased towards innate immunity and, albeit in homeostatic proliferation, their clonal expansion and effector functions are diminished (Galindo-Albarran et al, 2016). Lower mitochondria mass and membrane potential, as well as differences in calcium fluxes and in calcium and potassium channels have been reported (Meszaros et al, 2015;Palin et al, 2013;Toldi et al, 2010).…”